A screening tool developed at the University of Strathclyde, UK, could increase the number of tests on a solid tumor sample by up to 50 times.
The tool facilitates large-scale testing of the latest immunotherapies, such as Chimeric Antigen Receptor (CAR) T-cell therapy, which is effective against many hematological cancers but presents challenges when used to treat solid tumors.
Currently-used, traditional 2D models fail to reproduce the complexity of the tumor's microenvironment, while models based on patients' tumors are costly and labor-intensive; 3D models reproduce significantly better what happens in the body.
The Strathclyde-led study has developed a miniaturized platform for screening 3D tumor models to evaluate the toxicity of CAR-T therapy towards cells. The platform enabled visualization and quantification of how CAR-T cells rapidly targeted, broke up and killed cancer cells without causing significant harm to other cells.
In addition, the research found that, while chemotherapy treatment did not act specifically on cancer cells when used alone, treatment efficacy was enhanced when combined with CAR-T cell treatment.
Combination therapies represent a huge opportunity for cancer medicine and this technology will aid pharma companies' efforts to look for new treatments.
The study also involved researchers at the University of Glasgow and the Cancer Research UK Beatson Institute in Glasgow, led by Dr Seth Coffelt. The work has been published in the IEEE Open Journal of Engineering in Medicine and Biology.
The research was led by Dr Michele Zagnoni, a Reader in Strathclyde's Department of Electronic and Electrical Engineering, and recently graduated PhD student Karla Paterson.
Dr Zagnoni said: "There are particular challenges with evaluating solid tumors, not just cancerous cells but those surrounding them.
We are developing a technology platform which could accelerate the development of therapies and provide models which are much more representative of what happens in the body than what is currently available.
We are providing a platform for labs to conduct tests before proceeding to clinical trials, that uses fewer resources and can scale up cost-effectively.
CAR-T cell development is expensive and patient-derived tissue is a limited resource. Our aim is to enable 20 to 50 times more experiments to be performed in these conditions."
Dr Michele Zagnoni, a Reader in Strathclyde's Department of Electronic and Electrical Engineering
The technology is to be commercialized by ScreenIn3D, a pre-spinout company co-founded in 2018 by Dr Zagnoni, who is the company's CEO, and Alex Sim, who is its Executive Chair. Karla Paterson is working for the company as an Application Specialist, along with Jolanta Beinarovica. It was established with the support of Strathclyde's IP & Commercialisation team.
This study stems from a larger project that was recently named joint winner of Strathclyde's Stephen Young Entrepreneurship Award for an Outstanding Business Idea Research Paper. The award was established through a £50 million gift made to the University in 2021 by the Charles Huang Foundation; £20 million of entrepreneur and philanthropist Dr Huang's gift was made to honour Professor Young, who died in August 2021 and who was Dr Huang's PhD supervisor and mentor during his studies at Strathclyde.
The research received funding from AMS Biotechnology Europe Ltd (AMSBIO).
Through the activities of its Health and Care Futures initiative, the University of Strathclyde uses its expertise and state-of-the-art innovation in the fields of medicines innovation, health technologies, data analytics and artificial intelligence, and the workforce and leadership to make an effective and sustained contribution to the future of health and care in the UK and beyond.
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Journal reference:
Paterson, K., et al. (2022) Assessment of CAR-T Cell-Mediated Cytotoxicity in 3D Microfluidic Cancer Co-Culture Models for Combination Therapy. IEEE Open Journal of Engineering in Medicine and Biology. doi.org/10.1109/OJEMB.2022.3178302.